The understanding of molecular identification and molecular mechanisms regarding proliferation, apoptosis, differentiation, etc., leads to the understanding of malignant transformation and pathological conditions of cells. Modifications of molecular function (molecular target) focusing on particular genes or signal channels are one of methods for artificially controlling dynamics of cells and normalizing pathological conditions of cells.
Many anti-cancer agents as have been applied so far are derived from natural substances and chemical compounds. They, however, have drawbacks that they may react to cancer cells and to normal cells, too, causing severe side effects. Recent years, therefore, trials have been made of clinical applications of molecular target agents with the attempt to reduce such side effects, however, the current state of such molecular target agents is not yet satisfactory in terms of efficacy and reduction of side effects.
ZFAT gene (zinc-finger gene in autoimmune thyroid disease susceptibility region: ZNF406) identified as a gene associated with autoimmune thyroid diseases is a Zn finger protein coding for a protein composed of 1,243 amino acid residues and having one AT hook domain and 18 Zn finger domains. The distribution of the ZFAT proteins in mouse tissues is characterized in that it is strongly expressed in the thymus gland and the spleen yet the expressing cells are limited to B cells and T cells (Non-Patent Literature No. 1). The mechanism of ZFAT protein is not yet identified.
RNAi (RNA interference) is noted as an effective method for analyzing genetic functions. RNAi is a phenomenon in that a double-stranded RNA (dsRNA) consisting of a sense RNA and an anti-sense RNA, homologous to a gene, destroys a homologous portion of a transcription product (mRNA) of the gene, thus leading to inhibition of the expression of a gene having a sequence identical thereto, that is, to inhibition of the synthesis of a protein (for example, Non-patent Literature Nos. 2, 3, 4). In other words, RNAi is a unique method that can search for functions of genes by performing a knock-out of (destroying) mRNA of a target gene having a known sequence.
Further, RNAi can confirm results at a cell level so that it is advantageous to achieve result in more precise way, at lower costs and in shorter time, compared to conventional gene knock-out method that confirms results using animals. In addition thereto, the RNAi method has the merits that results can be expected to be achieved at a low concentration, and only mRNA can be destroyed without affecting any adverse influence on the genomic gene itself.    [Non-patent Literature No. 1] Koyanagi, M., Nakabayashi, K., Fujimoto, T., Gu, N., Baba, I., Takashima, Y., Doi, K., Harada, H., Kato, N., Sasazuki, T., and Shirasawa, S. (2008) Genomics 91, 451-457    [Non-patent Literature No. 2] Fire, A/, et al: Nature (1998) 391:806-811    [Non-patent Literature No. 3] Ui-Tei, K., et al: FEBS Lett (2000) 479: 79-82    [Non-patent Literature No. 4] Elbashir S M., et al: Nature (2001) 411:494-498